ABSTRACT This proposed longitudinal investigation builds on, and significantly extends, our preliminary work focused on health-related quality-of-life (HRQoL) among sibling pediatric hematopoietic stem cell (HSC) donors. Although the use of minors as HSC donors is medically and legally accepted, recent policy statements by the American Academy of Pediatrics and our own preliminary work which found pediatric donor HRQoL deficits indicate that additional research in this area is critical. Our preliminary work found that ~20% of healthy pediatric donors experienced clinically important HRQoL deficits shortly before and up to one year following donation. In addition, parents over-estimated HRQoL of the donor child and this overestimation was particularly large for children with the poorest self-reported HRQoL. The overarching goal of this proposed investigation is to identify predictors of poor HRQoL among some sibling pediatric HSC donors. In addition, we will identify the most productive potential targets for, and content of, interventions or guideline changes to improve HRQoL. The study will generate a new, large cohort of sibling pediatric donors, their recipients and caregivers and three non-donor comparison groups. We will conduct interviews at pre-donation, and 4 weeks, 6 months and 1 year post-donation with 409 sibling pediatric HSC donors, their recipients and parents and three key comparison groups ? all nondonor siblings age 5-18 from the same family, nondonor siblings of patients receiving unrelated transplants, and a matched sample of healthy comparisons. Medical data from donors, recipients and transplant center data will be collected and merged with interview data. Analyses focus on hypotheses derived from the existing literature, our own preliminary work, and a multivariable model to determine which donor, recipient, family and center characteristics predict donor HRQoL. This investigation is significant because (a) pediatric HSC donation is increasing, (b) it focuses on a vulnerable group of healthy children being asked to undergo potential medical/psychological risk with no direct self-benefit, (c) it will provide critical information about predictors of poor HRQoL among pediatric donors, (d) it will disentangle whether observed HRQoL deficits are due to the donation process, to family dynamics, and/or to some other aspect of having a critically ill sibling, and (e) it will provide the basis for guidelines/interventions to mitigate the risk of poor donor HRQoL. The investigation is innovative because it will be the first to (a) examine pediatric HSC donor HRQoL in a large nationwide sample, (b) provide important and novel comparisons with nondonor children, (c) use an innovative application of group-based trajectory modeling to examine donor HRQoL, (d) comprehensively evaluate the effects of donor/recipient/family/transplant factors on pediatric donor HRQoL and (e) include a large ethnically diverse and Spanish-speaking sample. This investigation will advance our understanding of HRQoL among sibling pediatric HSC donors and their families and provide crucial information for the development of guidelines/interventions for this group.